Could gut microbiota help early-stage detection of colorectal cancer?

Colorectal cancer (also known as bowel cancer) is the third most common cancer in the world, according to World Cancer Research Fund International. By 2035, it is predicted there will be 2.4 million cases of this type of tumour diagnosed annually worldwide, mostly in developed countries. The risk of developing it is about 1 in 20 (5%) and it is one of the three leading causes of cancer-related deaths.

Most colon cancers are sporadic, meaning they are not inherited genetically. As such, environmental and lifestyle risk factors may play an important role in the development of colorectal cancer. It is well known that the earlier this cancer is detected, the better the outcome. Until now, a colonoscopy remains the gold standard for early screening as it provides the best view of the entire inner colon. Nevertheless, it is a very invasive test and a significant percentage of adults are reluctant to undergo this procedure.

Now, a team of researchers may have discovered a new, potentially non-invasive screening tool based on individuals’ gut microbiota, which could be used as a complement to colonoscopies and other screening tests.

“Different research groups, us included, have hypothesised that gut microbiota, considered a major environmental factor for our health, may play a role in colon cancer,” explained to Gut Microbiota Worldwatch Julien Tap, a microbial ecologist and data analyst at the MetaGenoPolis project and co-author of the study published in Molecular System Biology. In previous studies, abnormalities in this microbial community have been reported to be linked to obesity, inflammatory bowel disease (IBD) and colorectal cancer. Nevertheless, the bacterial community inhabiting our gut has never been explored for potential screening to detect early-stage tumours.

The researchers collected stool samples from 61 healthy people, 53 patients with advanced colon or rectal cancer and 42 people with precancerous intestinal polyps. It is important to remark that scientists asked subjects to give those samples days to weeks before they had bowel cleaning for a colonoscopy, as they suspected it could impact the gut microbiota composition, including bias for any metagenomics test.

By performing stool DNA sequencing and bioinformatics analysis, they characterised the gut microbiota from patients’ stool samples and found different features of the bacterial population in each group of individuals. Researchers also collected information on body mass index, age and ethnicity – three factors known to also influence colorectal cancer.

Their findings revealed both enrichment and a depletion of several populations of bacteria that were related to adenomas and carcinomas. “A study published in 2013 by Kostic and colleagues showed how Fusobacterium nucleatum potentiates intestinal tumourgenesis and modulates the tumour-immune microenvironment. In our study, we actually found that certain specific subspecies of Fusobacterium nucleatum are particularly enriched in colon cancer patients. We validated this with an independent cohort including 335 patients from different countries,” said Tap.

The proposed gut microbiota test is aimed at complementing existing screening procedures, such as Faecal Occult Blood Test (FOBT). Researchers found that the ability to detect the presence of precancerous and cancerous lesions was improved when they combined both methods and included subjects’ demographic data.

“If we use them [metagenomics and FOBT tests] together, sensibility increases more than 45% over the FOBT test alone. The metagenomics test actually provides different information compared to the FOBT test. We even showed that the metagenomics test has the potential to be more sensitive for early stages of colon cancer compared to the FOBT test. This last point is important as the chance of survival is higher when colon cancer is treated early,” highlighted Tap.

If these results are confirmed in a larger population study, they may lead to a new non-invasive stool test that could very efficiently and effectively screen for colon cancer and even precancerous lesions. “In the future, we could even imagine sequencing our DNA and our metagenomes using an USB pen-like device, so all findings highlighted in our study could be translated into a routine service in local laboratories, with low costs,” claimed Tap.

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